Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer
Luis Paz-Ares, Alexander Luft, David Vicente, Ali Tafreshi, Mahmut Gümüş, Julien Mazières, Barbara Hermes, Filiz Çay Şenler, Tibor Csőszi, Andrea Fülöp, Jerónimo Rodríguez-Cid, Jonathan Wilson, Shunichi Sugawara, Terufumi Kato, Ki Hyeong Lee, Ying Cheng, Silvia Novello, Balazs Halmos, Xiaodong Li, Gregory M Lubiniecki, Bilal Piperdi, Dariusz M Kowalski, KEYNOTE-407 Investigators, Baerin Ben Houghton, Rina Hui, Ross Jennens, Nathalie Aucoin, Vincent Castonguay, Andrew Robinson, Jocelyn Roy, Stephanie Snow, Giovanna Speranza, Flavia De Angelis, Lejie Cao, Hongjun Gao, Yubiao Guo, Zhigang Han, Chengping Hu, Jie Hu, Meijuan Huang, Xiaoling Li, Jiwei Liu, Zhiyong Ma, Hong Sun, Donglin Wang, Ziping Wang, Lin Wu, Shiying Yu, Helong Zhang, Li Zhang, Jianying Zhou, Romain Corre, Sophie Cousin, Ludovic Doucet, Louis-Marie Dourthe, Sandrine Hiret, Denis Moro-Sibilot, Xavier Quantin, Arnaud Scherpereel, Luc Thiberville, Walburga Engel-Riedel, Wolfram Gruening, Jens Kollmeier, Konrad Kokowski, Ernst Spaeth-Schwalbe, Beatrix Balint, Ildiko Horvath, Balazs Medgyasszay, Sandor Tehenes, Ettore D’Argento, Rosanna Berardi, Luca Gianni, Vincenzo Minotti, Danilo Rocco, Hector Soto Parra, Hiroaki Akamatsu, Keisuke Aoe, Shinji Atagi, Tatsuro Fukuhara, Tomonori Hirashima, Hidehito Horinouchi, Yukio Hosomi, Masao Ichiki, Fumio Imamura, Reiko Kaji, Kazuo Kasahara, Kazuma Kishi, Kaoru Kubota, Takayasu Kurata, Yasuharu Nakahara, Makoto Nishio, Naoyuki Nogami, Kadoaki Ohashi, Morihito Okada, Isamu Okamoto, Hideo Saka, Miyako Satouchi, Toshiaki Takahashi, Hiroshi Tanaka, Takaaki Tokito, Hibiki Udagawa, Takuma Yokoyama, Eleazar Macedo-Perez, Emmanuel de la Mora Jimenez, Bonne Biesma, Frank Custers, M M van den Heuvel, Ewa Kalinka-Warzoch, Boguslawa Karaszewska, Rodryg Ramlau, Lyudmila Kuzina, Konstantin Laktionov, Guzel Mukhametshina, Vladimir Vladimirov, Jin Hyoung Kang, Bong-Seog Kim, Gyeong-Won Lee, Sung Sook Lee, Young Joo Min, Begona Campos, Enriqueta Felip, Margarita Majem, Bartomeu Massuti, Ana Ortega, Mariano Provencio, Jose Trigo, Arunee Dechaphunkul, Krittiya Korphaisarn, Naiyarat Prasongsook, Thanyanan Reungwetwattana, Virote Sriuranpong, Irfan Cicin, Mustafa Erman, Seyda Gunduz, Hakan Harputluoglu, Metin Ozkan, Ilhan Oztop, Hande Turna, Sinan Yavuz, Dan Costin, Konstantin Dragnev, Herbert Duvivier, Edward B Garon, Greg Gerstner, Mark Graham, Richard Gralla, Michael J Guarino, Elise Hattersley-Anderes, Anthony Jaslowski, Robert Jotte, Stephan DiSean Kendall, Goetz Kloecker, Tarek Mekhail, Mahsa Mohebtash, Andrew Parchman, Suman Banner Rao, Sreekanth Reddy, Francisco Robert, Igor I Rybkin, Edgardo Santos, Gene Saylors, Bethany Graham Sleckman, Matei Socoteanu, Laura Stampleman, James Stevenson, William V Walsh, David Waterhouse, John Wrangle, Luis Paz-Ares, Alexander Luft, David Vicente, Ali Tafreshi, Mahmut Gümüş, Julien Mazières, Barbara Hermes, Filiz Çay Şenler, Tibor Csőszi, Andrea Fülöp, Jerónimo Rodríguez-Cid, Jonathan Wilson, Shunichi Sugawara, Terufumi Kato, Ki Hyeong Lee, Ying Cheng, Silvia Novello, Balazs Halmos, Xiaodong Li, Gregory M Lubiniecki, Bilal Piperdi, Dariusz M Kowalski, KEYNOTE-407 Investigators, Baerin Ben Houghton, Rina Hui, Ross Jennens, Nathalie Aucoin, Vincent Castonguay, Andrew Robinson, Jocelyn Roy, Stephanie Snow, Giovanna Speranza, Flavia De Angelis, Lejie Cao, Hongjun Gao, Yubiao Guo, Zhigang Han, Chengping Hu, Jie Hu, Meijuan Huang, Xiaoling Li, Jiwei Liu, Zhiyong Ma, Hong Sun, Donglin Wang, Ziping Wang, Lin Wu, Shiying Yu, Helong Zhang, Li Zhang, Jianying Zhou, Romain Corre, Sophie Cousin, Ludovic Doucet, Louis-Marie Dourthe, Sandrine Hiret, Denis Moro-Sibilot, Xavier Quantin, Arnaud Scherpereel, Luc Thiberville, Walburga Engel-Riedel, Wolfram Gruening, Jens Kollmeier, Konrad Kokowski, Ernst Spaeth-Schwalbe, Beatrix Balint, Ildiko Horvath, Balazs Medgyasszay, Sandor Tehenes, Ettore D’Argento, Rosanna Berardi, Luca Gianni, Vincenzo Minotti, Danilo Rocco, Hector Soto Parra, Hiroaki Akamatsu, Keisuke Aoe, Shinji Atagi, Tatsuro Fukuhara, Tomonori Hirashima, Hidehito Horinouchi, Yukio Hosomi, Masao Ichiki, Fumio Imamura, Reiko Kaji, Kazuo Kasahara, Kazuma Kishi, Kaoru Kubota, Takayasu Kurata, Yasuharu Nakahara, Makoto Nishio, Naoyuki Nogami, Kadoaki Ohashi, Morihito Okada, Isamu Okamoto, Hideo Saka, Miyako Satouchi, Toshiaki Takahashi, Hiroshi Tanaka, Takaaki Tokito, Hibiki Udagawa, Takuma Yokoyama, Eleazar Macedo-Perez, Emmanuel de la Mora Jimenez, Bonne Biesma, Frank Custers, M M van den Heuvel, Ewa Kalinka-Warzoch, Boguslawa Karaszewska, Rodryg Ramlau, Lyudmila Kuzina, Konstantin Laktionov, Guzel Mukhametshina, Vladimir Vladimirov, Jin Hyoung Kang, Bong-Seog Kim, Gyeong-Won Lee, Sung Sook Lee, Young Joo Min, Begona Campos, Enriqueta Felip, Margarita Majem, Bartomeu Massuti, Ana Ortega, Mariano Provencio, Jose Trigo, Arunee Dechaphunkul, Krittiya Korphaisarn, Naiyarat Prasongsook, Thanyanan Reungwetwattana, Virote Sriuranpong, Irfan Cicin, Mustafa Erman, Seyda Gunduz, Hakan Harputluoglu, Metin Ozkan, Ilhan Oztop, Hande Turna, Sinan Yavuz, Dan Costin, Konstantin Dragnev, Herbert Duvivier, Edward B Garon, Greg Gerstner, Mark Graham, Richard Gralla, Michael J Guarino, Elise Hattersley-Anderes, Anthony Jaslowski, Robert Jotte, Stephan DiSean Kendall, Goetz Kloecker, Tarek Mekhail, Mahsa Mohebtash, Andrew Parchman, Suman Banner Rao, Sreekanth Reddy, Francisco Robert, Igor I Rybkin, Edgardo Santos, Gene Saylors, Bethany Graham Sleckman, Matei Socoteanu, Laura Stampleman, James Stevenson, William V Walsh, David Waterhouse, John Wrangle
Abstract
Background: Standard first-line therapy for metastatic, squamous non-small-cell lung cancer (NSCLC) is platinum-based chemotherapy or pembrolizumab (for patients with programmed death ligand 1 [PD-L1] expression on ≥50% of tumor cells). More recently, pembrolizumab plus chemotherapy was shown to significantly prolong overall survival among patients with nonsquamous NSCLC.
Methods: In this double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, 559 patients with untreated metastatic, squamous NSCLC to receive 200 mg of pembrolizumab or saline placebo for up to 35 cycles; all the patients also received carboplatin and either paclitaxel or nanoparticle albumin-bound [nab]-paclitaxel for the first 4 cycles. Primary end points were overall survival and progression-free survival.
Results: After a median follow-up of 7.8 months, the median overall survival was 15.9 months (95% confidence interval [CI], 13.2 to not reached) in the pembrolizumab-combination group and 11.3 months (95% CI, 9.5 to 14.8) in the placebo-combination group (hazard ratio for death, 0.64; 95% CI, 0.49 to 0.85; P<0.001). The overall survival benefit was consistent regardless of the level of PD-L1 expression. The median progression-free survival was 6.4 months (95% CI, 6.2 to 8.3) in the pembrolizumab-combination group and 4.8 months (95% CI, 4.3 to 5.7) in the placebo-combination group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.45 to 0.70; P<0.001). Adverse events of grade 3 or higher occurred in 69.8% of the patients in the pembrolizumab-combination group and in 68.2% of the patients in the placebo-combination group. Discontinuation of treatment because of adverse events was more frequent in the pembrolizumab-combination group than in the placebo-combination group (13.3% vs. 6.4%).
Conclusions: In patients with previously untreated metastatic, squamous NSCLC, the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel resulted in significantly longer overall survival and progression-free survival than chemotherapy alone. (Funded by Merck Sharp & Dohme; KEYNOTE-407 ClinicalTrials.gov number, NCT02775435 .).
Source: PubMed